Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis.

Fangmin Huang, Jiankun Liang, Yingying Lin, Yushi Chen, Fen Hu, Jianting Feng, Qiang Zeng, Zeteng Han, Qiaofa Lin, Yan Li, Jingyi Li, Lanqin Wu, Lisheng Li

Communications biology 2023 Sep 23

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Necroptosis is a form of regulated cell death that has been implicated in multiple diseases. TNF-induced necroptosis is regulated by necrosomes, complexes consisting of RIPK1, RIPK3 and MLKL. In this study, by screening of a small-compound library, we identified dozens of compounds that inhibited TNF-induced necroptosis. According to the mechanisms by which they inhibited necroptosis, these compounds were classified into different groups. We then identified Ibrutinib as an inhibitor of RIPK3 and found that Quizartinib protected against the TNF-induced systemic inflammatory response syndrome in mice by inhibiting the activation of RIPK1. Altogether, our work revealed dozens of necroptosis inhibitors, suggesting new potential approaches for treating necroptosis-related diseases. © 2023. Springer Nature Limited.

Citation

Fangmin Huang, Jiankun Liang, Yingying Lin, Yushi Chen, Fen Hu, Jianting Feng, Qiang Zeng, Zeteng Han, Qiaofa Lin, Yan Li, Jingyi Li, Lanqin Wu, Lisheng Li. Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis. Communications biology. 2023 Sep 23;6(1):972